The invention relates to adjustment systems and computer readable-mediums that can be used in time-of-flight mass spectrometry (TOFMS) to account for thermal drift. Methods of adjusting time-of-flight mass spectra to account for thermal drift or mechanical strain are also provided.
In time-of-flight mass spectrometry (TOFMS), one calculates the mass-to-charge ratio (m/z) of ions by measuring their velocities. Typically the ion charge is one (z=1), and thus we speak of ion masses instead of mass-to-charge ratios. Ions of varying masses are separated by their differing velocities as they travel along a field-free path of known length. Similarly, xe2x80x9cmass scalexe2x80x9d is typically used to refer to the assignment of masses to flight times and xe2x80x9cmass spectrumxe2x80x9d refers to a list of ion abundances and corresponding ion masses.
Time-of-flight mass spectrometers are described, for example, in U.S. Pat. Nos. 4,490,610; 5,463,220; and 5,614,711. Ion abundances for each mass are measured as ions strike a detector at the end of the path. The signal acquired from the detector shows these ion abundances as a function of travel time.
The following mathematical relationship can be used to convert travel time (t) to ion mass (m):
t=c+k{square root over (m)}xe2x80x83xe2x80x83Equation (1) 
where k is a constant related to the length of the flight path and the ion energy and c is a small delay time which may be introduced by the signal cable and/or detection electronics.
For very high accuracy, however, it is desirable to model the ion motion with a more complex expression having more than two parameters. In general, mass is related to time by a model such as
m=f(a0,a1, . . . an,t0,t)xe2x80x83xe2x80x83Equation (2) 
Here a0, . . . an are coefficients and t0 is a time offset. Thus, mass is a function of a set of parameters (e.g., a0, a1, etc.), optionally including a time offset parameter (t0) and flight time t.
Typically, an equation of the following form is used:                               m                =                                            a              0                        +                                          a                1                            ⁢              t                        +                                          a                2                            ⁢                              t                2                                      +                          …              ⁢                              xe2x80x83                            ⁢                              a                n                            ⁢                              t                n                            ⁢                              xe2x80x83                            ⁢              or              ⁢                              xe2x80x83                            ⁢                              m                                              =                                    a              0                        +                                          ∑                                  i                  =                  1                                n                            ⁢                                                a                  i                                ⁢                                  t                  i                                                                                        Equation        ⁢                  xe2x80x83                ⁢                  (          3          )                    
To calculate ion mass, the value of the calibration parameters a0, a1, . . . an must be determined. Typically, this is done by measuring times ti for several known masses mi and fitting the model to this data. The higher order terms a2 . . . an are small corrections which are often neglected if high accuracy is not required. Mass accuracies of 10 parts-per-million (ppm) or better are often necessary, however, for analysis of peptides and other compounds of biological interest.
Generally, a large number of influences affect the stability of the mass scale calibration curve: inconstancy of the high voltages for acceleration of the ions, variable spacing of the acceleration diaphragms in the ion source caused by the mounting of sample supports introduced into the vacuum, variable initial energies of the ions due to the ionization process, and not least, thermal changes in the length of the flight path. U.S. Pat. No. 6,049,077 describes the use of special materials to construct time-of-flight mass spectrometers in order to compensate for thermal expansion.
During operation, the temperature of a mass spectrometer can vary by 10 degrees Celsius or more. In particular, the power source (e.g., electronics) and other factors can lead to increased temperatures which, in turn, can affect the resulting mass calibration. In order to keep the mass spectra as accurate as possible, the addition of internal references is often used. However, this solution is inconvenient, as it requires the addition of mass-similar references for each sample. Furthermore, use of special, temperature-controlling materials is costly and has no opportunity for feedback.
Thus, there remains a need for methods, devices and systems to compensate for thermal drift and/or mechanical strain in time-of-flight mass spectrometry.
In one aspect, the invention includes a method for adjusting a mass spectrum for a sample to account for temperature changes or mechanical strain in a time-of-flight mass spectrometer. Typically, the method comprises the steps of (a) obtaining a temperature or strain measurement from a time-of-flight mass spectrometer; (b) selecting calibration parameters that describe the mass spectrum at the temperature or strain measurement obtained in step (a); and (c) using a mathematical model comprising the calibration parameters selected in step (b) to provide an adjusted mass spectrum for a sample ion to account for temperature changes or mechanical strain.
In another aspect, an adjustment system for adjusting a mass spectrum obtained from a time-of-flight mass spectrometer to account for thermal drift or strain is provided. An adjustment system for adjusting a mass spectrum obtained from a time-of-flight mass spectrometer to account for thermal drift or strain can comprise a computing means (or one or more computer readable mediums) in operative communication with at least one temperature or mechanical strain sensor to obtain temperature or strain readings from at least one position in the time-of-flight mass spectrometer. Preferably, the computing means is capable of adjusting mass scale based on the readings using a mathematical model comprising calibration parameters and the calibration parameters describe the adjusted mass scale.
In another aspect, the invention includes an article of manufacture comprising a computer usable medium having computer readable program medium embodied therein for causing calibration parameters of Equation (3) to be adjusted to account for thermal drift or mechanical strain in order to obtain mass spectra data.
In yet another aspect, the invention includes a computerized method for accounting for thermal drift or mechanical strain in a time-of-flight mass spectrometer, comprising: (a) maintaining a database of calibration parameters for use in determining mass spectra at a particular temperature or strain measurement; (b) selecting the appropriate calibration parameters from the database to determine a mass spectrum of a sample subject to time-of-flight mass spectrometry and during which mass spectrometry the temperature or strain is monitored; and (c) controlling a user interface to display or print the mass spectrum which has adjusted to account for thermal drift or mechanical strain.
In another aspect, the invention includes a computer-readable medium having computer-executable instructions for performing a method comprising: (a) maintaining a database of calibration parameters for use in determining mass spectra at a particular temperature or strain measurement; (b) selecting the appropriate calibration parameters from the database to determine a mass spectrum of a sample subject to time-of-flight mass spectrometry and during which mass spectrometry the temperature or strain is monitored; and (c) controlling a user interface to display or print the mass spectrum which has been adjusted to account for thermal drift or mechanical strain.
In any of the methods or systems (e.g., methods, adjustment systems, articles of manufacture, computerized methods, computer-readable mediums) described herein, the temperature (or strain) measurement is preferably obtained using at least one sensor in the time-of-flight mass spectrometer, for example, at least one sensor in the flight chamber, in the power supply and/or in the electronic components which produce the ion accelerating voltage pulse. Furthermore, in certain embodiments, the calibration parameters are determined from first principles or, alternatively, the calibration parameters are determined empirically, for example by solving the calibration parameters of Equation (3) using a known mass sample at a range of temperatures or mechanical strains. When determined empirically, the calibration parameters are determined for a known mass sample at various temperature intervals, for example for at least every degree between 15 and 65 degrees Celsius, and preferably for at least every half of degree between 20 and 30 degrees Celsius.
These and other embodiments of the subject invention will readily occur to those of skill in the art in light of the disclosure herein.